Moleculin Biotech announced additional positive interim safety and efficacy data from one of the Company's two ongoing open label, single arm Phase 1/2 studies of Annamycin for the treatment of relapsed or refractory acute myeloid leukemia (AML).
The Phase 1 portion of these clinical trials is designed to establish the safety of Annamycin and to determine the Recommended Phase 2 Dose to be used in the Phase 2 portion of the trials. While the Primary Endpoint of the Phase 1 portion is safety, a Secondary Endpoint is the assessment of efficacy generally defined as an improvement in bone marrow biopsy results sufficient to qualify patients for a potentially curative bone marrow transplant. The Company cautions not to place undue reliance on interim results.
The third cohort in Poland receiving a single dose of 180 mg/m2 in the Phase 1 dose escalation portion of the trial was completed with no adverse events and the trial will continue to the next cohort of 210 mg/m2. In the US trial, one patient has completed treatment in the second cohort at 120 mg/m2. This brings the total number of patients treated and evaluated at or above 120 mg/m2 to 10. An additional patient in the US has begun treatment at 120 mg/m2 but has yet to complete post-treatment evaluation. The interim results for these 10 patients are 1 CRi (defined as a complete response with incomplete recovery of white blood cells and/or platelets) and 2 partial responses ("PRs" or where bone marrow blasts are reduced 50% and to below 25%). One additional patient was bridged to bone marrow transplant (BT) based on a sufficient reduction in bone marrow blasts, bringing the total to 4 out of 10 patients at or above 120 mg/m2 who have demonstrated efficacy.
In the latest cohort in Poland, 1 of the 3 patients treated at 180 mg/m2 had a PR sufficient to qualify for a potentially curative bone marrow transplant. The results for all 3 patients were reviewed by the Safety Review Committee, which determined that no drug-related adverse events were observed that would prevent advancing the trial to the next higher dose level of 210 mg/m2. To date in the European trial, only one adverse event related to Annamycin has been reported; a patient experienced grade 2 mucositis (which resolved to grade 1 within 2 days). In the Company's parallel US clinical trial, one new patient (the first of cohort #2) achieved a "morphologically leukemia free state" or MLFS, which also constitutes a CRi, after receiving a single dose of 120 mg/m2.
The company is referring to Annamycin as a "next generation anthracycline," because it is designed to provide enhanced therapeutic benefits when compared with traditional anthracyclines (like doxorubicin) while reducing the potential for unwanted cardiotoxicity, or damage to the heart. This design intent has previously been validated with preclinical toxicology studies in animal models (as required by FDA) demonstrating Annamycin has little to no cardiotoxicity when compared with doxorubicin. Of the 14 patients treated thus far in both trials, none has shown any evidence of cardiotoxicity. This includes 7 patients in Poland who were treated at levels above the US maximum allowable cumulative anthracycline dose level (550 mg/m2), a limitation not imposed on our trial in Europe. If upheld in further studies, this lack of toxicity could be an important differentiator between Annamycin and the currently approved anthracyclines, for which cardiotoxicity is a well-known treatment limitation.
"The interim data from our early-stage clinical trials of Annamycin continues to meet or exceed our expectations, from both a safety and efficacy perspective," said Walter Klemp, Moleculin's Chairman and CEO. "We believe the activity we are seeing – with 40% of patients treated at or above 120 mg/m2 responding with CRi's, PR's and/or bridging to a potentially curative bone marrow transplant – is encouraging, especially since we have yet to reach a maximum tolerable dose. Although the data is preliminary, we are excited by the results to date, and to continue moving forward. Importantly, recruitment continues to be much faster in Europe than in the US. We believe this is because Europe has imposed fewer regulatory constraints on the level of anthracycline dosing allowed and because there are far fewer competing AML clinical trials in Poland, wher...
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